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Thoracic outlet syndrome is a challenging clinical condition in terms of diagnosis, treatment, and health-related quality of life assessment. In this review, the authors provide a description of the clinical approach, surgical management, and longitudinal follow-up for patients with neurogenic, venous, and arterial thoracic outlet syndrome. The review represents the experiences of a high-volume, dedicated thoracic outlet syndrome program, where patients are treated in a multidisciplinary team and operative decompression occurs through primarily a supraclavicular approach. Data supporting the safety and efficacy of this approach are provided, as are clinical care considerations for surgeons treating patients with thoracic outlet syndrome.
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Descompressão Cirúrgica , Síndrome do Desfiladeiro Torácico , Síndrome do Desfiladeiro Torácico/cirurgia , Síndrome do Desfiladeiro Torácico/diagnóstico , Humanos , Descompressão Cirúrgica/métodos , Resultado do Tratamento , Clavícula , Qualidade de VidaRESUMO
The purpose of this study was to identify the response of biomolecules and biomarkers that are associated with the central nervous system to aerobic exercise in human and pre-clinical models of concussion or mild traumatic brain injury (TBI), and to highlight the knowledge gaps in the literature. A systematic scoping review was conducted following a search of EMBASE, MEDLINE, SCOPUS, BIOSIS, and Cochrane Libraries performed on September 8, 2023 (from data base inception). The scoping review was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews. Duplicates were removed and article screening was performed using an online systematic review management system. The search resulted in a total of 2,449 articles being identified, with 14 articles meeting the inclusion/exclusion criteria and having their data extracted. One study was conducted in humans, while the remainder of identified studies utilized murine models. The current literature is limited and evaluated many different biomolecules and biomarkers with brain-derived neurotrophic factor being the most researched. Further studies on this topic are needed to better understand the biomarker response to exercise after concussion and mild TBI, especially in the human population.
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Dinoflagellates are an abundant and diverse group of protists representing a wealth of unique biology and ecology. While many dinoflagellates are photosynthetic or mixotrophic, many taxa are heterotrophs, often with complex feeding strategies. Compared to their photosynthetic counterparts, heterotrophic dinoflagellates remain understudied, as they are difficult to culture. One exception, a long-cultured isolate originally classified as Amphidinium but recently reclassified as Oxytoxum, has been the subject of a number of feeding, growth, and chemosensory studies. This lineage was recently determined to be closely related to Prorocentrum using phylogenetics of ribosomal RNA gene sequences, but the exact nature of this relationship remains unresolved. Using transcriptomes sequenced from culture and three single cells from the environment, we produce a robust phylogeny of 242 genes, revealing Oxytoxum is likely sister to the Prorocentrum clade, rather than nested within it. Molecular investigations uncover evidence of a reduced, nonphotosynthetic plastid and proteorhodopsin, a photoactive proton pump acquired horizontally from bacteria. We describe the ultrastructure of O. lohmannii, including densely packed trichocysts, and a new type of mucocyst. We observe that O. lohmannii feeds preferentially on cryptophytes using myzocytosis, but can also feed on various phytoflagellates using conventional phagocytosis. O. lohmannii is amenable to culture, providing an opportunity to better study heterotrophic dinoflagellate biology and feeding ecology.
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BACKGROUND: Despite continuing advancements in treatments for opioid use disorder (OUD), continued high rates of relapse indicate the need for more effective approaches, including novel pharmacological interventions. Glucagon-like peptide 1 receptor agonists (GLP-1RA) provide a promising avenue as a non-opioid medication for the treatment of OUD. Whereas GLP-1RAs have shown promise as a treatment for alcohol and nicotine use disorders, to date, no controlled clinical trials have been conducted to determine if a GLP-1RA can reduce craving in individuals with OUD. The purpose of the current protocol was to evaluate the potential for a GLP-1RA, liraglutide, to safely and effectively reduce craving in an OUD population in residential treatment. METHOD: This preliminary study was a randomized, double-blinded, placebo-controlled clinical trial designed to test the safety and efficacy of the GLP-1RA, liraglutide, in 40 participants in residential treatment for OUD. Along with taking a range of safety measures, efficacy for cue-induced craving was evaluated prior to (Day 1) and following (Day 19) treatment using a Visual Analogue Scale (VAS) in response to a cue reactivity task during functional near-infrared spectroscopy (fNIRS) and for craving. Efficacy of treatment for ambient craving was assessed using Ecological Momentary Assessment (EMA) prior to (Study Day 1), across (Study Days 2-19), and following (Study Days 20-21) residential treatment. DISCUSSION: This manuscript describes a protocol to collect clinical data on the safety and efficacy of a GLP-1RA, liraglutide, during residential treatment of persons with OUD, laying the groundwork for further evaluation in a larger, outpatient OUD population. Improved understanding of innovative, non-opioid based treatments for OUD will have the potential to inform community-based interventions and health policy, assist physicians and health care professionals in the treatment of persons with OUD, and to support individuals with OUD in their effort to live a healthy life. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04199728. Registered 16 December 2019, https://clinicaltrials.gov/study/NCT04199728?term=NCT04199728 . PROTOCOL VERSION: 10 May 2023.
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Fissura , Sinais (Psicologia) , Avaliação Momentânea Ecológica , Receptor do Peptídeo Semelhante ao Glucagon 1 , Liraglutida , Transtornos Relacionados ao Uso de Opioides , Humanos , Fissura/efeitos dos fármacos , Método Duplo-Cego , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Liraglutida/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Feminino , Masculino , Adulto , Tratamento Domiciliar/métodos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
INTRODUCTION: Drawbacks of fixed-output spinal cord stimulation (SCS) screening trials may lead to compromised trial outcomes and poor predictability of long-term success. Evoked compound action potential (ECAP) dose-controlled closed-loop (CL) SCS allows objective confirmation of therapeutic neural activation and pulse-to-pulse stimulation adjustment. We report on the immediate patient-reported and neurophysiologic treatment response post-physiologic CL-SCS and feasibility of early SCS trial responder prediction. METHODS: Patient-reported pain relief, functional improvement, and willingness to proceed to permanent implant were compared between the day of the trial procedure (Day 0) and end of trial (EOT) for 132 participants in the ECAP Study undergoing a trial stimulation period. ECAP-based neurophysiologic measurements from Day 0 and EOT were compared between responder groups. RESULTS: A high positive predictive value (PPV) was achieved with 98.4% (60/61) of patients successful on the Day 0 evaluation also responding at EOT. The false-positive rate (FPR) was 5.6% (1/18). ECAP-based neurophysiologic measures were not different between patients who passed all Day 0 success criteria ("Day 0 successes") and those who did not ("needed longer to evaluate the therapy"). However, at EOT, responders had higher therapeutic usage and dose levels compared to non-responders. CONCLUSIONS: The high PPV and low FPR of the Day 0 evaluation provide confidence in predicting trial outcomes as early as the day of the procedure. Day 0 trials may be beneficial for reducing patient burden and complication rates associated with extended trials. ECAP dose-controlled CL-SCS therapy may provide objective data and rapid-onset pain relief to improve prognostic ability of SCS trials in predicting outcomes. TRIAL REGISTRATION: The ECAP Study is registered with ClinicalTrials.gov (NCT04319887).
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Background Acute subdural hematomas commonly require emergent surgical decompression by craniotomy. There is currently limited research on alternative surgical strategies in the elderly population. This study investigates delayed surgical intervention for stable patients with low-energy trauma presenting with acute subdural hematomas. Methodology In this retrospective chart review, 45 patients over the age of 55 presenting with acute subdural hematomas with a Glasgow Coma Scale score greater than or equal to 13 in the setting of low-energy trauma were selected. Additionally, included patients had a maximal hematoma thickness of >10 mm and/or a midline shift size of >5 mm per the current Brain Trauma Foundations guidelines for surgical intervention of subdural hematomas. The study was performed at a large tertiary care center, with records being examined from 1995 to 2020. Comparison groups were immediate craniotomy (within 24 hours) or delayed burr hole (minimum of 48 hours passing since the initial presentation). Primary outcomes included minor complications, major complications, any complications, and any complications with mortality excluded. There was no significant difference in mortality between the two cohorts. Results The immediate craniotomy group consisted of 16 patients, while the delayed burr hole group consisted of 29 patients. The results demonstrated a statistically significant increase in the incidence of any complication including mortality (relative risk (RR) = 3.17, 95% confidence interval (CI) = 1.71-5.88, p < 0.0001), major complications (RR = 2.33, 95% CI = 1.07-5.07, p = 0.031), and minor complications (RR = 2.42, 95% CI = 1.02-5.74, p = 0.041) in the immediate craniotomy group compared to the delayed burr hole group. Conclusions Our study demonstrates the decreased risk of major and minor complications for delayed burr hole evacuation in stable patients >55 years old presenting with low-energy trauma and subdural hematoma. The results suggest that for this population of patients, it appears to be beneficial to delay surgery if the patient's clinical situation allows.
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Skeletal muscle plays an integral role in locomotion, but also as part of the integrative physiological system. Recent progress has identified crosstalk between skeletal muscle and various physiological systems, including the immune system. Both the musculoskeletal and immune systems are impacted by aging. Increased age is associated with decreased muscle mass and function, while the immune system undergoes "inflammaging" and immunosenescence. Exercise is identified as a preventative medicine that can mitigate loss of function for both systems. This review summarizes: (1) the inflammatory pathways active in skeletal muscle; and (2) the inflammatory and skeletal muscle response to unaccustomed exercise in younger and older adults. Compared to younger adults, it appears older individuals have a muted pro-inflammatory response and elevated anti-inflammatory response to exercise. This important difference could contribute to decreased regeneration and recovery following unaccustomed exercise in older adults, as well as in chronic disease. The current research provides specific information on the role inflammation plays in altering skeletal muscle form and function, and adaptation to exercise; however, the pursuit of more knowledge in this area will delineate specific interventions that may enhance skeletal muscle recovery and promote resiliency in this tissue particularly with aging.
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Envelhecimento , Exercício Físico , Inflamação , Músculo Esquelético , Humanos , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiologia , Músculo Esquelético/imunologia , Envelhecimento/fisiologia , Inflamação/metabolismo , Exercício Físico/fisiologia , AnimaisRESUMO
Mate choice is a key trait that determines fitness for most sexually reproducing organisms, with females often being the choosy sex. Female preference often results in strong selection on male traits that can drive rapid divergence of traits and preferences between lineages, leading to reproductive isolation. Despite this fundamental property of female mate choice, very few loci have been identified that contribute to mate choice and reproductive isolation. We used a combination of population genetics, quantitative complementation tests, and behavioural assays to demonstrate that alan shepard and Neuroglian contribute to female mate choice, and could contribute to partial reproductive isolation between populations of Drosophila melanogaster. Our study is among the first to identify genes that contribute to female mate preference in this historically important system, where female preference is an active premating barrier to reproduction. The identification of loci that are primarily known for their roles in neurodevelopment provides intriguing questions of how female mate preference evolves in populations via changes in sensory system and higher learning brain centres.
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Proteínas de Drosophila , Drosophila melanogaster , Preferência de Acasalamento Animal , Animais , Drosophila melanogaster/genética , Drosophila melanogaster/fisiologia , Feminino , Proteínas de Drosophila/genética , Masculino , Isolamento ReprodutivoRESUMO
BACKGROUND: Inebilizumab, an anti-CD19 B-cell-depleting antibody, demonstrated safety and efficacy in neuromyelitis optica spectrum disorder in the randomised controlled period of the N-MOmentum trial. Here, end-of-study data, including the randomised controlled period and open-label extension period, are reported. METHODS: In the double-blind, randomised, placebo-controlled, phase 2/3 N-MOmentum trial, adults aged 18 years and older with an neuromyelitis optica spectrum disorder diagnosis, Expanded Disability Status Scale score of 8·0 or less, and history of either at least one acute inflammatory attack requiring rescue therapy in the past year or two attacks requiring rescue therapy in the past 2 years, were recruited from 81 outpatient specialty clinics or hospitals in 24 countries. Eligible participants were randomly assigned (3:1), using a central interactive voice system or interactive web response system, and a permuted block randomisation scheme (block size of 4), to receive intravenous inebilizumab (300 mg) or identical placebo on days 1 and 15 of the randomised period, which lasted up to 197 days. Participants and all study staff were masked to treatment assignment. The primary endpoint of the randomised period of the trial was time to onset of adjudicated neuromyelitis optica spectrum disorder attack on or before day 197. Participants in the randomised controlled period who had an adjudicated attack, completed 197 days in the study, or were in the randomised controlled period when enrolment stopped, could voluntarily enter the open-label period. In the open-label period, participants either initiated inebilizumab if assigned placebo (receiving 300 mg on days 1 and 15 of the open-label period) or continued treatment if assigned inebilizumab (receiving 300 mg on day 1 and placebo on day 15, to maintain B-cell depletion and masking of the randomised controlled period). All participants subsequently received inebilizumab 300 mg every 6 months for a minimum of 2 years. The end-of-study analysis endpoints were time to adjudicated attack and annualised attack rate (assessed in all participants who received inebilizumab at any point during the randomised controlled period or open-label period [any inebilizumab population] and the aquaporin-4 [AQP4]-IgG seropositive subgroup [any inebilizumab-AQP4-IgG seropositive population]) and safety outcomes (in all participants who were exposed to inebilizumab, analysed as-treated). This study is registered with ClinicalTrials.gov, NCT02200770, and is now complete. FINDINGS: Between Jan 6, 2015, and Sept 24, 2018, 467 individuals were screened, 231 were randomly assigned, and 230 received at least one dose of inebilizumab (n=174) or placebo (n=56). Between May 19, 2015, and Nov 8, 2018, 165 (95%) of 174 participants in the inebilizumab group and 51 (91%) of 56 in the placebo group entered the open-label period (mean age 42·9 years [SD 12·4], 197 [91%] of 216 were female, 19 [9%] were male, 115 [53%] were White, 45 [21%] were Asian, 19 [9%] were American Indian or Alaskan Native, and 19 [9%] were Black or African American). As of data cutoff for this end of study analysis (Dec 18, 2020; median exposure 1178 days [IQR 856-1538], total exposure of 730 person-years) 225 participants formed the any inebilizumab population, and 208 (92%) participants were AQP4-IgG seropositive. Overall, 63 adjudicated neuromyelitis optica spectrum disorder attacks occurred in 47 (21%) of 225 treated participants (60 attacks occurred in 44 [21%] of 208 in the AQP4-IgG seropositive subgroup); 40 (63%) of 63 attacks occurred in 34 (15%) of 225 treated participants during the first year of treatment. Of individuals who had an adjudicated attack while receiving inebilizumab, 36 (77%) of 47 were subsequently attack-free at the end of 4 years. Annualised attack rates decreased year-on-year, with end-of-study adjusted annualised attack rates being similar in the any inebilizumab-AQP4-IgG seropositive subgroup (0·097 [95% CI 0·070-0·14]) and any inebilizumab populations (0·092 [0·067-0·13]). Overall, 208 (92%) of 225 participants who received any inebilizumab had at least one treatment-emergent adverse event, the most frequent of which were urinary tract infection (59 [26%]), nasopharyngitis (47 [21%]), and arthralgia (39 [17%]). Infection rates did not increase over 4 years. Three (1%) of 225 participants in the any inebilizumab population died during the open-label period (one each due to a CNS event of unknown cause and pneumonia, respiratory insufficiency resulting from an neuromyelitis optica spectrum disorder attack and viral pneumonia related to COVID-19), all of which were deemed to be unrelated to treatment. INTERPRETATION: Data from the end-of-study analysis of the N-MOmentum trial showed continued and sustained clinical benefits of long-term inebilizumab treatment in individuals with neuromyelitis optica spectrum disorder, which supports the role of inebilizumab as a CD19+ B-cell-depleting therapy in neuromyelitis optica spectrum disorder. FUNDING: MedImmune and Viela Bio/Horizon Therapeutics, now part of Amgen.
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Anticorpos Monoclonais Humanizados , Neuromielite Óptica , Humanos , Neuromielite Óptica/tratamento farmacológico , Feminino , Adulto , Masculino , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Método Duplo-Cego , Pessoa de Meia-Idade , Resultado do Tratamento , Idoso , Adulto JovemRESUMO
BACKGROUND: The minimum weight for enterostomy closure (EC) in infants remains debated with the current acceptable cut-off of >2 kg. As enterostomy-related complications or high enterostomy output (>30cc/kg/d) may prohibit a premature infant from reaching 2 kg, additional data is needed to evaluate the safety of EC in infants <2 kg. The objective of this study was to evaluate postoperative outcomes in low body weight (<2 kg) infants undergoing EC compared to larger infants. METHODS: We performed a multi-center retrospective analysis from 1/1/2012-12/31/2022 of all infants (age <1 year) who were <4 kg at time of EC. Primary outcomes included postoperative complications and 30-day mortality. Non-parametric analysis was performed using the Kruskal-Wallis one-way analysis of variance and chi-square tests. Univariable logistic regression was performed to identify factors associated with postoperative complications. RESULTS: Of 92 infants, 15 infants (16.3%) underwent EC at <2 kg, 16 (17.4%) at 2-2.49 kg, 31 (33.7%) at 2.5-2.99 kg, and 30 (32.6%) at ≥3 kg. Infants <2 kg at time of EC exhibited higher rates of hyperbilirubinemia (P = .030), neurologic comorbidities (P = .030), and high enterostomy output (P = .041). There was no difference in postoperative complications (P = .460) or 30-day mortality (P = .460) between the <2 kg group and larger weight groups. Low body weight was not associated with an increased risk for developing a postoperative complication (OR: 1.001, 95% CI: 1.001-1.001; P = .032). CONCLUSION: Our findings suggest that EC in infants <2 kg may be safe with comparable postoperative outcomes to larger weight infants. Thus, the timing of EC should be based on the infant's physiologic status, in contrast to a predetermined minimum weight cut-off.
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Instances of convergent or parallel evolution provide a potent model system for exploring contingency and determinism in evolutionary biology. Likewise, the multiple, independent habitat transitions from saltwater to freshwater biomes offer opportunity for studying convergent evolution within and among different vertebrate lineages. For example, stingrays have invaded freshwater habitats multiple times across different continents, sometimes even several times within the same clade (e.g., Dasyatidae). We evaluated the frequency of saltwater-freshwater invasions in stingrays, compared ecological and phenotypic diversification among freshwater and saltwater lineages, and assessed the degree of convergence among freshwater species. Despite not being morphologically distinct from saltwater stingrays, freshwater stingrays do expand the margins of stingray morphological diversity. According to our data, trophic specialists occupied non-overlapping regions of morphospace, with piscivores and molluscivores being distinct from other diet guilds. Freshwater stingrays as a group did not strongly converge morphologically, neither did freshwater rays from different lineages which shared similar niches. These findings could be explained by there not being enough time for convergence to occur among more ancient and more recent freshwater lineages. Alternatively, the different ancestral bauplans of various freshwater ray lineages and weak selection on optimal phenotypes could promote contingency in the form of evolution along paths of least resistance.
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Background: Left ventricular aneurysms (LVAs) are a well-appreciated complication of acute myocardial infarction. Ventricular aneurysms involving the left ventricle (LV) typically evolve as a result of anterior myocardial infarction and are associated with greater morbidity, complication rates, and hospital resource utilization. Incidence of LVA is decreasing with advent of modern reperfusion therapies; however, in the setting of excess morbidity, clinicians must maintain an appreciation for their appearance to allow timely diagnosis and individualized care. Case summary: This case report describes the clinical history, investigation, appearance, and management of a patient with calcified apical LVA with history of previous anterior ST-elevation myocardial infarction. The patient was initially admitted for elective coronary angiography in the setting of worsening exertional dyspnoea and subsequently underwent coronary artery bypass graft, aneurysm resection, and LV reconstruction. Discussion: Left ventricular aneurysms are an uncommon complication experienced in the modern era of acute myocardial infarction and current reperfusion therapies, but remain an important cause of excess morbidity and complication. Evidence-based guidelines for the diagnosis, workup, and subsequent management of LVAs are lacking. The imaging findings presented in this case serve as an important reminder of the appearance of LVAs so that timely diagnosis and individualized care considerations can be made.
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Magnetic van der Waals (vdW) materials have opened new frontiers for realizing novel many-body phenomena. Recently NiPS3 has received intense interest since it hosts an excitonic quasiparticle whose properties appear to be intimately linked to the magnetic state of the lattice. Despite extensive studies, the electronic character, mobility, and magnetic interactions of the exciton remain unresolved. Here we address these issues by measuring NiPS3 with ultra-high energy resolution resonant inelastic x-ray scattering (RIXS). We find that Hund's exchange interactions are primarily responsible for the energy of formation of the exciton. Measuring the dispersion of the Hund's exciton reveals that it propagates in a way that is analogous to a double-magnon. We trace this unique behavior to fundamental similarities between the NiPS3 exciton hopping and spin exchange processes, underlining the unique magnetic characteristics of this novel quasiparticle.
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It is well-documented that childhood socioeconomic status (SES) is associated with various health conditions in adulthood. Here, we examine the extent to which childhood SES is associated with COVID-19 pandemic anxiety and depression. Participants (n = 212), recruited from Amazon Mechanical Turk, were assessed for depression and anxiety in February 2022 for both the current context and retrospective self-perceived early pandemic depression and anxiety (April 2020). Participants also reported childhood SES and current demographics. Consistent with predated findings, we show a strong, positive correlation between depression and anxiety under both conditions. Paternal unemployment in childhood was associated with increased anxiety, while maternal occupation was not. High household education in childhood was generally associated with greater anxiety and depression, similar to past studies examining education levels and depression. However, the shift from high school to post-secondary degrees (trade school and associate's) was associated with decreased anxiety and depression, which may reflect "essential work" careers, therefore indicating a dualism. Growing up in crowded, de-individualized spaces was associated with lower anxiety and depression, suggesting better conditioning for the imposition of COVID-19 quarantines. Pandemic-related unemployment was associated with an increase in anxiety and depression. Strong political views, regardless of ideology, were associated with increased anxiety. Finally, participants in our cohort perceived their mental health to be worse in the early pandemic for anxiety and depression, up 6.6% and 7.9%, respectively. Our work suggests a complex relationship between SES, demographics, and anxiety and depression during the pandemic. These findings emphasize the importance of exploring the dynamics between early SES and mental health in adulthood, particularly during extended societal stressors.
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Hierarchical structure-within-structure assemblies offer a route toward increasingly complex and multifunctional materials while pushing the limits of block copolymer self-assembly. We present a detailed study of the self-assembly of a series of fluorinated high-χ block copolymers (BCPs) prepared via postmodification of a single poly(styrene)-block-poly(glycidyl methacrylate) (S-b-G) parent polymer with the fluorinated alkylthiol pendent groups containing 1, 6, or 8 fluorinated carbons (termed trifluoro-ethanethiol (TFET), perfluoro-octylthiol (PFOT), and perfluoro-decylthiol (PFDT), respectively). Bulk X-ray scattering of thermally annealed samples demonstrates hierarchical molecular assembly with phase separation between the two blocks and within the fluorinated block. The degree of ordering within the fluorinated block is highly sensitive to synthetic variation; a lamellar sublattice was formed for S-b-GPFOT and S-b-GPFDT. Thermal analyses of S-b-GPFOT reveal that the fluorinated block exhibits liquid crystal-like ordering. The complex thin-film self-assembly behavior of an S-b-GPFOT polymer was investigated using real-space (atomic force microscopy and scanning electron microscopy) and reciprocal-space (resonant soft X-ray scattering (RSoXS), grazing incidence small- and wide-angle scattering) measurements. After thermal annealing in nitrogen or vacuum, films thicker than 1.5 times the primary lattice spacing exhibit a 90-degree grain boundary, exposing a thin layer of vertical lamellae at the free interface, while exhibiting horizontal lamellae on the preferential (polystyrene brush) substrate. RSoXS measurements reveal the near-perfect orthogonality between the primary and sublattice orientations, demonstrating hierarchical patterning at the nanoscale.
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Goal: Dynamically monitoring serotonin in real-time within target brain regions would significantly improve the diagnostic and therapeutic approaches to a variety of neurological and psychiatric disorders. Current systems for measuring serotonin lack immediacy and portability and are bulky and expensive. Methods: We present a new miniaturised device, named SmartFSCV, designed to monitor dynamic changes of serotonin using fast-scan cyclic voltammetry (FSCV). This device outputs a precision voltage potential between -3 to +3 V, and measures current between -1.5 to +1.5 µA with nano-ampere accuracy. The device can output modifiable arbitrary waveforms for various measurements and uses an N-shaped waveform at a scan-rate of 1000 V/s for sensing serotonin. Results: Four experiments were conducted to validate SmartFSCV: static bench test, dynamic serotonin test and two artificial intelligence (AI) algorithm tests. Conclusions: These tests confirmed the ability of SmartFSCV to accurately sense and make informed decisions about the presence of serotonin using AI.
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BACKGROUND AND OBJECTIVES: In spinal cord stimulation (SCS) therapy, electricity is the medication delivered to the spinal cord for pain relief. In contrast to conventional medication where dose is determined by desired therapeutic plasma concentration, there is lack of equivalent means of determining dose delivery in SCS. In open-loop (OL) SCS, due to the dynamic nature of the epidural space, the activating electric field delivered is inconsistent at the level of the dorsal columns. Recent Food and Drug Administration guidance suggests accurate and consistent therapy delivered using physiologic closed-loop control (PCLC) devices can minimize underdosage or overdosage and enhance medical care. PCLC-based evoked compound action potential (ECAP)-controlled technology provides the ability to prescribe a precise stimulation dose unique to each patient, continuously measure neural activation, and objectively inform SCS therapy optimization. METHODS: Neurophysiological indicator metrics of therapy dose, usage above neural activation threshold, and accuracy of SCS therapy were assessed for relationship with pain reduction in over 600 SCS patients. RESULTS: Significant relationships between objective metrics and pain relief across the patient population are shown, including first evidence for a dose-response relationship in SCS. CONCLUSIONS: Higher dose, more time over ECAP threshold, and higher accuracy are associated with better outcomes across patients. There is potential to optimize individual patient outcomes based on unique objective measurable electrophysiological inputs.
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Nitrogen in wastewater has negative environmental, human health, and economic impacts but can be recovered to reduce the costs and environmental impacts of wastewater treatment and chemical production. To recover ammonia/ammonium (total ammonia nitrogen, TAN) from urine, we operated electrochemical stripping (ECS) for over a month, achieving 83.4 ± 1.5% TAN removal and 73.0 ± 2.9% TAN recovery. With two reactors, we recovered sixteen 500-mL batches (8 L total) of ammonium sulfate (20.9 g/L TAN) approaching commercial fertilizer concentrations (28.4 g/L TAN) and often having >95% purity. While evaluating the operation and maintenance needs, we identified pH, full-cell voltage, product volume, and water flux into the product as informative process monitoring parameters that can be inexpensively and rapidly measured. Characterization of fouled cation exchange and omniphobic membranes informs cleaning and reactor modifications to reduce fouling with organics and calcium/magnesium salts. To evaluate the impact of urine collection and storage on ECS, we conducted experiments with urine at different levels of dilution with flush water, extents of divalent cation precipitation, and degrees of hydrolysis. ECS effectively treated urine under all conditions, but minimizing flush water and ensuring storage until complete hydrolysis would enable energy-efficient TAN recovery. Our experimental results and cost analysis motivate a multifaceted approach to improving ECS's technical and economic viability by extending component lifetimes, decreasing component costs, and reducing energy consumption through material, reactor, and process engineering. In summary, we demonstrated urine treatment as a foothold for electrochemical nutrient recovery from wastewater while supporting the applicability of ECS to seven other wastewaters with widely varying characteristics. Our findings will facilitate the scale-up and deployment of electrochemical nutrient recovery technologies, enabling a circular nitrogen economy that fosters sanitation provision, efficient chemical production, and water resource protection.